Arsenic trioxide (As2O3) is a main component in the traditional Chinese medicine White Arsenic, and had been used to treat many diseases such as malignant tumor in Chinese medical science.
Natural arsenic compounds have been used as a medicine for more than 2400 years. In 1970s, hematologists used As2O3 to treat promyelocytic leukemia and notable therapeutic effect was obtained. As2O3 has also been used to treat solid tumor in recent years. Zhuoqi ZHANG et. al. and Jianwei SHAO et. al. found that As2O3 had effects of anti-proliferation, apoptosis promotion and cell cycle arrest on VSMCs, and was significant for possibly decreasing cell amount in the new tunica intima at the sites where blood vessel scaffold was implanted in vivo and reducing the thickness of the tunica intima.
On the premise of ensuring medical effect, to reduce the dosage of arsenic trioxide, a highly toxic medicine, as much as possible and to ensure the stability of the medicine amount carried on the scaffold so as to achieve suitable uniformity and controllability for arsenic trioxide release is critical in determining the use value of the arsenic trioxide elution scaffold.
Because of the difference in solubility between the water-soluble medicine arsenic trioxide and the polymer carrier, a characteristic two-phase separation is present during the spraying of the medicine and the carrier. For example, both of the arsenic trioxide spraying techniques disclosed in CN200510023714.5 and CN1413594A employ a process of spraying the medicine and the carrier together after mixing in a solvent. In these techniques, the control of the medicine amount on the scaffold and the uniformity of medicine distribution are restricted due to the settlement of arsenic trioxide (reduction in particle size of arsenic trioxide particles may induce conglomeration of the particles), and irregular channels may form among medicine particles, whereby it is difficult to control the stability of medicine release (see FIG. 1). This leads to a high-dosage of the medicine, poor efficacy on restenosis inhibition, and increased risk in clinical treatment. Several hours after damaging the blood vessel, scaffold and balloon dilatation may stimulate hyperplasia of SMC, which is beneficial for the formation of new tunica intima; several days to several months after the damage, relative deficiency of cell apoptosis during this period is an important reason for formation of restenosis. Therefore, it is necessary to provide desirable and stable medicine release on the scaffold.